Genomics-guided identification of potential modulators of SARS-CoV-2 entry proteases, TMPRSS2 and Cathepsins B/L

SARS-CoV-2 requires serine protease, transmembrane protease 2 (TMPRSS2), and cysteine proteases, cathepsins B, L (CTSB/L) for entry into host cells. These proteases activate the spike protein enable entry. We herein performed genomic-guided gene set enrichment analysis (GSEA) to identify upstream regulatory elements altering expression of TMPRSS2 CTSB/L. Further, medicinal compounds were identified based on their effects signatures modulators CTSB/L genes. Using this strategy, estradiol retinoic acid have been as putative alleviation agents. Next, we analyzed drug-gene gene-gene interaction networks using 809 human targets proteins. The network results indicate that interacts with 370 (45%) 251 (31%) Interestingly, a combination 461 (56%) proteins, indicating therapeutic benefits drug therapy. Finally, molecular docking suggests both drugs bind CTSL nanomolar low micromolar affinity. suggest these can simultaneously target pathways thus be considered potential treatment option COVID-19.